Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoma in adults.  The R-CHOP immunochemotherapy protocol has been the first-line standard of care for DLBCL patients for decades and is curative in approximately two-thirds of patients. However, 30–40% of patients are refractory or relapsing and they second-line salvage therapy that consisted of platinum-based chemotherapy regimens followed by autologous hematopoietic stem cell transplantation with curative intent for transplant-eligible patients or palliative chemotherapy for transplant-ineligible patients. The overall response rate is ranged between 40 to 60%. The median survival is approximately 13 months and the prognosis is even poorer for those who do not respond to salvage chemotherapy. Therefore, there is still an unmet need for these patients. Better understanding of both molecular biology of lymphoma cells and the tumor microenvironment have initiated clinical trials exploring targeted therapy based on driver genetic alterations. In recent years, several new therapeutic agents have been approved for the treatment of relapsed/refractory DLBCL. These agents include monoclonal antibodies such as polatuzumab vedotin (targeting CD79a), tafasitamab and loncastuximab tesirine (targeting CD 19), Selinexor (SINE inhibitor), anti-CD19 chimeric antigen receptor T-cell therapies and bispecific antibodies.